SINGAPORE -- A pump structure on the surface of cells in a bat may be the key to their ability to accumulate fewer toxic chemicals than human cells.
The cell surface pump protein, known as ABCB1, is more abundant and widely distributed in bat tissue than in humans and may be the reason bats have fewer cancers, say researchers from Duke-NUS Medical School.
“Our team investigated the unique anti-cancer mechanisms in bats and found that exposure to toxic drugs caused significantly less DNA damage in bat cells than human cells due to the presence of the important ABCB1 protein,” said Associate Professor Koji Itahana, from Duke-NUS’ Cancer and Stem Cell Biology Programme.
DNA damage in cells can contribute to cancer in many ways. The researchers discovered decreased drug accumulation in cells due to greater amounts of ABCB1 across multiple bat species.
The investigations also blocked ABCB1 in bat cells and triggered the accumulation of toxic chemicals, causing more DNA damage and cell death.
“Our findings reveal that the transportation of toxic drugs out of the system protects bat cells from DNA damage, which may contribute to their low cancer incidence,” said Professor Wang Linfa, director of the Emerging Infectious Diseases Programme at Duke-NUS. “This discovery can provide important insights into cancer biology that can be translated into future therapies for humans.”
Human tumor cells have been found to acquire elevated amounts of the ABCB1 pump protein in response to prolonged chemotherapy, which may be one of the major causes of drug resistance. The research team is currently working on developing drugs that can be less toxic to ABCB1, which could be used to overcome drug resistance in human cancer.
Drug resistance arising from chemotherapy is still one of the main reasons for cancer recurrence and patient death.
Professor Patrick Casey, Senior Vice Dean of Research at Duke-NUS, commented, “It is estimated that one in every four to five people in Singapore may develop cancer in their lifetime, and the number of people living with cancer will continue to increase. This important study exemplifies how the cross-fertilization of ideas and collaboration among researchers with different specializations can yield important insights that may lead to future strategies to prevent or treat cancer.”
This research was supported by the National Research Foundation of Singapore (NRF2012NRF-CRP001-056).
CITATION: “ABCB1 protects bat cells from DNA damage induced by genotoxic compounds,” Koh J, Itahana Y, Mendenhall IH, Low D, Soh EXY, Guo AK, Chionh YT, Wang LF and Itahana K. Nature Communications, June 27, 2019. DOI: 10.1038/s41467-019-10495-4.
https://www.nature.com/articles/s41467-019-10495-4